Recognizing Unusual Tumors Part 3: Sebaceous Lesions and Carcinoma

George H. Martin

Sebaceous neoplasms have long been a source of confusion to dermatologists and there are disagreements regarding nomenclature, classification, and best approaches to management.  These lesions include hamartomas, hyperplasias, and benign tumors, as well as highly malignant neoplasms.  Specific sebaceous lesions include sebaceous hyperplasia, nevus sebaceous of Jadassohn, sebaceous adenoma, seboacanthoma, sebaceous epithelioma, sebaceoma, mantleoma, basal cell carcinoma with sebaceous differentiation, sebomatricoma (sebomatrixoma), and sebaceous carcinoma (Eisen, 2009).

Sebaceous Gland Carcinoma (SGC)

SGC is an uncommon adnexal neoplasm with a well-documented capacity for regional and distant metastasis. Historically, SGC has been associated with high rates of recurrence after excision (Kyllo, 2015).  This tumor is thought to arise from sebaceous glands in the skin and, thus, may occur anywhere on the body where these glands are present.  About three-fourths of these tumors arise in the periocular region, an area rich in sebaceous glands (Wu, 2016).

SGC: Eyelid

This tumor accounts for 1-5% of eyelid malignancies, it occurs more frequently in women than men, and arises most often in the 6th-7th decade of life.  It exhibits an aggressive clinical course, with a significant tendency for both local recurrence and distant metastasis.  It usually appears as a painless, slowly enlarging nodule that is yellowish to pink/red color. Diagnosis of ocular SGC is often significantly delayed because it mimics several benign eye conditions, including chalazion, keratoconjunctivitis, blepharoconjunctivitis, and ocular pemphigoid (Wali, 2010).

Suspect SGC when you see:

  • Non resolving chalazion:
    • Inflammation of the Meibomian glands or glands of Zeis
    • Painless granulomatous inflammation
    • Most common misdiagnosis of sebaceous carcinoma
  • Loss of cilia
  • Yellow streaks on conjunctiva
  • Increased vascularity
  • Chronic unilateral inflammation

Extraorbital SGC

Despite the widespread anatomic distribution of sebaceous glands, extraorbital SGC is very rare comprising only 25% of all reported cases for these tumors (Mathur, 2010). Extraocular SGCs most commonly involve the head and neck region, in which sebaceous glands are most plentiful, followed by external genitalia, the parotid and submandibular glands, the external auditory canal, the trunk and upper extremity, sole, the dorsum of the great toe, and laryngeal or pharyngeal cavities (Mathur, 2010). The most frequent clinical presentation is a painless subcutaneous nodule, but it can also present as pedunculated lesions, an irregular mass, or diffuse thickening of the skin. This variable presentation often results in confusion with benign tumors or inflammatory conditions, including basal cell carcinoma (BCC), cutaneous cell carcinoma, squamous cell carcinoma, ceratoacanthoma, cornu cutaneum and Bowen’s disease, as well numerous other malignant and benign lesions thereby leading to delay in diagnosis, inappropriate treatment, increased morbidity, and mortality (Natarajan, 2011; Bolm, 2015).

Muir-Torre Syndrome

Muir-Torre syndrome (MTS) is a rare autosomal dominant genodermatosis that predisposes individuals to skin tumors and visceral malignancies. MTS is very rare, with only about 200 cases reported. Males are more commonly affected, with a male to female ratio of 3:2, and individuals can present at any age. Sebaceous tumors precede visceral malignancy diagnosis in 22% of patients, occur simultaneously in 6%, and develop subsequently in 56% of reported MTS cases (Bhaijee, 2014). MTS-related sebaceous tumors include sebaceous adenoma, sebaceoma/sebaceous epithelioma, sebaceous carcinoma, keratoacanthoma with sebaceous differentiation, BCC with sebaceous differentiation, and cystic sebaceous neoplasms (Bhaijee, 2014).

This cancer is potentially very aggressive and close cancer surveillance is required in individuals with MTS and their families (John, 2016).  The majority of MTS is caused by a mutation in one of the mismatch repair gene (MHL1, MLH2, or MHL3) (Bhaijee, 2014).  However, a newly described subtype of MTS does not demonstrate microsatellite instability and may be inherited in an autosomal recessive pattern. In addition, MTS may be unmasked in transplant recipients taking specific immunosuppressant drugs or other immunosuppressed patients (John, 2016).

Patients can be screened for Muir-Torre Syndrome:

  • Testing sebaceous lesions for microsatellite instability
  • Immunohistochemical staining for mismatch repair genes

Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) was originally described by Toker in 1972 as trabecular carcinoma of the skin. Other names for this malignancy include Toker tumor, primary small cell carcinoma of the skin, primary cutaneous neuroendocrine tumor, and malignant trichodiscoma (NCI, 2015). MCC is an aggressive neuroendocrine carcinoma arising in the dermo-epidermal junction.  It was initially thought to be a sweat gland tumor until electron microscopic studies revealed cytoplasmic secretory granules in tumor cells (Munde, 2013). In Surveillance, Epidemiology and End Results Program data from 1986 to 2001, the age-adjusted United States annual incidence of MCC tripled from 0.15 to 0.44 per 100,000, an increase of 8.08% per year.  This rate of increase is faster than any other skin cancer including melanoma and the reason for it is not known (NCI, 2015).


The etiology of MCC is not fully understood, but in 2008, a novel polyomavirus (Merkel cell polyoma virus, MCPyV) was first reported in MCC tumor specimens. High levels of viral DNA and clonal integration of the virus in MCC tumors have also been reported. It has been suggested that there may be two independent pathways for the development of MCC: one driven by the presence of MCPyV and the other driven primarily by sun damage (Saini, 2015; Tothill, 2015).


MCC lesions are blue or red, firm, non-tender, solitary, dome-shaped nodules.

Occasional plaque-like or subcutaneous masses may also be observed.  Lesions are typically <2 cm, but they may reach 20 cm in size. MCC occurs most frequently in sun-exposed areas of skin, particularly the head and neck, followed by the extremities, and then the trunk with >25% of cases on the face (NCI, 2015). MCC can infiltrate locally via dermal lymphatics, resulting in multiple satellite lesions. Because of its nonspecific clinical appearance, MCC is rarely suspected prior to biopsy (NCI, 2015).


Histopathologically, monomorphic dermal and/or subcutaneous nodes are found consisting of round or oval medium sized cells with a vesicular nucleus and sparse cytoplasm. The neoplastic cells of MCC express cytokeratin (CK) 20 with a dot-like perinuclear accentuation. In addition, pan-CK, neuroendocrine markers (e.g., chromogranin A and synaptophysin), neurofilament proteins, CD56, CD57, Bcl-2, terminal deoxynucleotidyl transferase (TdT), and PAX-5 are immunohistochemically positive. CM2B4, an antibody against MCPyV is also positive in most tumors (Fried, 2014). Expression of p63 has been observed in some of the cases of MCC and has been associated with a poorer prognosis (Asioli, 2011).  It has also been shown that Ki-67 staining predicts poor outcomes in patients with MCC (Vujic, 2015). In contrast, overall survival is higher in patients with Bcl-2-positive tumors vs those with negative tumors (Sahi, 2012)

Sentinel Lymph Node Biopsy (SLNB)

Sentinel lymph node positivity is strongly predictive of high short-term risk for recurrence or metastasis in patients with MCC. A study carried out about 15 years ago indicated that therapeutic lymph node dissection appears effective in preventing short-term regional nodal recurrence and aggressive adjuvant treatment should be considered for patients with positive sentinel lymph nodes (Mehrany, 2002).  A more recent study that included 153 patients with localized MCC indicated that SLNB identifies occult nodal metastases in 29% of patients with localized MCC. Predictors of SLNB positivity are tumor size and presence of lymphovascular invasion (Fields, 2011).  Most recently, a record review for 161 patients with MCC treated at a single institution indicated that SLNB identified micrometastases in 33% of 27 early-stage patients. Recurrence developed in 56% of SLNB-positive vs 39% of SLNB-negative patients (Santamaria-Barria, 2013).

Immunohistochemical assessment of SLNBs from 10 patients with MCC indicated that all micrometastatic foci stained strongly for CK-20.  The authors of this study noted examination of hematoxylin and eosin (H&E) sections alone is insufficient for excluding micrometastatic MCC in sentinel lymph nodes and that staining for CK-20 has high sensitivity and specificity (Su, 2002).


Multidisciplinary treatment is essential to deliver optimal care to patients with MCC. Surgery involves a wide local excision with or without adjuvant therapy depending on the size of the primary lesion and stage of disease. There is controversy regarding the ideal margin width, and the National Comprehensive Cancer Network guidelines recommend 1–2 cm margins when feasible (NCCN, 2016). Mohs micrographic surgery has been employed as an alternative to wide local excision. Among the benefits of this approach are tissue conservation and identification of tumors that would otherwise require extremely wide excision margins (Boyer, 2002). Nevertheless, surgical resection of MCC with negative margins is the preferred primary modality of therapy when possible (Saini, 2015).

Radiation therapy can be considered for primary therapy in patients who are not surgical candidates. Postsurgical adjuvant radiation is often indicated in the treatment of MCC and is shown to improve outcomes (Saini, 2015).  However, data are conflicting as to whether there is any survival benefit from adjuvant primary site or regional nodal irradiation, partly due to the lack of prospective clinical trials (Prewett, 2015).  Chemotherapy is currently used in advanced stage MCC and as palliative therapy. There is no standard choice of chemotherapeutic agent (Saini, 2015).

Recent work also suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients (Cassler, 2016). First-line therapy with pembrolizumab in 26 patients with advanced MCC was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive and –negative tumors (Nghiem, 2016).

A treatment approach for patients with MCC:

  • Wide local excision (2 cm margins) or Mohs surgery
  • Sentinel lymph node biopsy with anti-CK20 antibody if H&E eosin is negative
  • For positive node:
    • Therapeutic node dissection
    • Adjuvant radiation and/or chemotherapy
  • Consider immunotherapy in patients with advanced disease


Asioli S, Righi A, de Biase D, et al. Expression of p63 is the sole independent marker of aggressiveness in localised (stage I-II) Merkel cell carcinomas. Mod Pathol. 2011;24:1451-1461.

Bhaijee F, Brown AS. Muir-Torre syndrome. Arch Pathol Lab Med. 2014;138:1685-1689.

Bolm I, Babaryka G, Moergel M, Al-Nawas B, Kämmerer PW. Multifocal metastasizing extra-ocular facial sebaceous carcinoma as diagnostic challenge: case report and systematic review. J Maxillofac Oral Surg. 2015;14 (Suppl 1):331-337.

Boyer JD, Zitelli JA, Brodland DG, D’Angelo G. Local control of primary Merkel cell carcinoma: review of 45 cases treated with Mohs micrographic surgery with and without adjuvant radiation. J Am Acad Dermatol. 2002;47:885-892.

Cassler NM, Merrill D, Bichakjian CK, Brownell I. Merkel Cell Carcinoma Therapeutic Update. Curr Treat Options Oncol. 2016;17:36.

Eisen DB, Michael DJ. Sebaceous lesions and their associated syndromes: part I J Am Acad Dermatol. 2009;61:549-560.

Fields RC, Busam KJ, Chou JF, et al. Recurrence and survival in patients undergoing sentinel lymph node biopsy for Merkel cell carcinoma: analysis of 153 patients from a single institution. Ann Surg Oncol. 2011;18:2529-2537.

Fried I, Cerroni L. Merkel cell carcinoma. Pathologe. 2014;35:467-75.

John AM, Schwartz RA. Muir-Torre syndrome (MTS): An update and approach to diagnosis and management. J Am Acad Dermatol. 2016;74:558-566.

Kyllo RL, Brady KL, Hurst EA. Sebaceous carcinoma: review of the literature. Dermatol Surg. 2015;41:1-15.

Mathur SK, Singh S, Rajni Y, Amrita R, Rajeev S. Extraocular sebaceous carcinoma – a rare tumour at a rare site. Egypt Dermatol Online J. 2010;6:14.

Mehrany K, Otley CC, Weenig RH, Phillips PK, Roenigk RK, Nguyen TH. A meta-analysis of the prognostic significance of sentinel lymph node status in Merkel cell carcinoma. Dermatol Surg. 2002;28:113-117.

Munde PB, Khandekar SP, Dive AM, Sharma A. Pathophysiology of Merkel cell. J Oral Maxillofac Pathol. 2013;17:408-412.

Natarajan K, Rai R, Pillai SB. Extra ocular sebaceous carcinoma: a rare case report. Indian Dermatol Online J. 2011;2:91-93.

National Comprehensive Cancer Network. Merkel Cell Carcinoma. Version I. 2016. Available at:

National Cancer Institute. PDQ Adult Treatment Editorial Board. Merkel Cell Carcinoma Treatment (PDQ®): Health Professional Version. 2015 Apr 9. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Available at:

Nghiem PT, Bhatia S, Lipson EJ, et al. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. N Engl J Med. 2016;374:2542-2552.

Prewett SL, Ajithkumar T. Merkel Cell Carcinoma: Current Management and Controversies. Clin Oncol (R Coll Radiol). 2015;27:436-444.

Sahi H, Koljonen V, Kavola H, et al. Bcl-2 expression indicates better prognosis of Merkel cell carcinoma regardless of the presence of Merkel cell polyomavirus. Virchows Arch. 2012;461:553-559.

Saini AT, Miles BA. Merkel cell carcinoma of the head and neck: pathogenesis, current and emerging treatment options. Onco Targets Ther. 2015;8:2157-2167.

Santamaria-Barria JA, Boland GM, Yeap BY, Nardi V, Dias-Santagata D, Cusack JC Jr. Merkel cell carcinoma: 30-year experience from a single institution. Ann Surg Oncol. 2013;20:1365-1373.

Tothill R, Estall V, Rischin D. Merkel cell carcinoma: emerging biology, current approaches, and future directions. Am Soc Clin Oncol Educ Book. 2015:e519-526.

Vujic I, Marker M, Posch C, et al. Merkel cell carcinoma: mitoses, expression of Ki-67 and bcl-2 correlate with disease progression. J Eur Acad Dermatol Venereol. 2015;29:542-548.

Wali UK, Al-Mujaini A. Sebaceous gland carcinoma of the eyelid. Oman J Ophthalmol. 2010;3:117-121.

Wu W. Dermatologic manifestations of sebaceous carcinoma. Medscape. 2016.

Infectious Disease 2016: Onychomycosis

Dr. Aditya K Gupta

Dr. Aditya K Gupta

Dr. Aditya K Gupta

Onychomycosis is an infection of the nail plate that is prevalent among the ageing population. Onychomycosis is difficult to treat with low initial cure rates, high rates of relapse, and reinfection. Changing demographic characteristics, such as the relative aging of the population, the increasing prevalence of diabetes and peripheral vascular disease, widespread iatrogenic immunosuppression, and changes in lifestyle (e.g., earlier and greater participation in sports), are likely to lead to an increased prevalence of onychomycosis in both adults and children. Mixed infections of dermatophytes and nondermatophyte molds are increasing in patients with onychomycosis. One recent case series indicated the presence of mixed infections in 41% of patients.

There have been a number of important advances in the treatment of onychomycosis.

New topical agents approved in the US for the treatment of onychomycosis are solutions with lower viscosity and increased nail penetration characteristics. These agents penetrate through the transungual route and via the space between the nail plate and the nail bed. The subungual route partially circumvents the thickness of the nail plate. Laser therapy has been promoted as one of the most promising device-based therapies for onychomycosis. Clinical trial and anecdotal results to date have varied greatly and the specific mechanism of action for this intervention has not been well-elucidated. Overall, this therapy provides cosmetic improvement, but is does not appear to treat the underlying disease. Combining nail drilling with antimycotic treatment has recently been shown to be effective for the treatment of onychomycosis. Treatment with holes plus topical terbinafine produces significantly greater improvement in toenails’ appearance and higher mycological cure rates compared to treating the dorsal aspect of the nail plate with topical terbinafine alone. Overall, early treatment is the path to cure in patients with onychomycosis. The chance of success is better when you treat early.

Recurrence (relapse or re-infection) occurs in 10% to 53% of patients of patients with onychomycosis. However, data on recurrence is limited by the fact that clinical studies have followed patients beyond 12 months. Although a number of factors have been suggested to play a role in recurrence, only the co-existence of diabetes has been shown to have a significant impact. A small study showed that amorolfine prophylaxis may delay recurrence, but prophylaxis may need to be continued for up to 3 years for optimal effect. Treating tinea pedis and any immediate family members may also decrease risk for recurrence; and other preventative strategies include avoiding communal areas where infection can spread and decontaminating footwear.

Maui Derm 2016 Highlights: Biosimilar Clinical Study Design, Extrapolation, and Interchangeability

B. Strober, MD, PhD

Is it really the same? The designs of clinical trials for biosimilars are very different from those for originator agents: sample sizes are smaller and durations are shorter. All of these studies are aimed at demonstrating equivalence between the biosimilar and the originator.

It is remarkable that approval for one indication may confer approval in all indications achieved by the reference product. The biosimilar may never be evaluated in a clinical trial before it is used in clinical practice. Given the compounds in question are far more complicated than a generic drug – it may be inappropriate for us to consider these as simply the “generics” of biologics.

Interchangeability may greatly affect your practice. This designation of a biosimilar based on additional evidence demonstrating that the biosimilar can be expected to produce the same clinical result as the reference product in any given patient. Interchangeability will support non-medical treatment changes in your patients mandated by pharmacists and payers.

Advanced Systemic and Topical Therapy in Pediatrics

A few clinical pearls from Dr. Albert Yan’s presentation on Advanced Systemic and Topical Therapy in Pediatrics at the 2015 Fall NPPA conference:

  • N-acetylcysteine compounded into a topical formulation may inhibit keratinocyte proliferation and help with keratinizing disorders (ichthyosis, and possibly epidermal nevi and PPK)
  • N-acetylcysteine administered systemically can be help in mediating glutamate metabolism and help with neuropsychiatric disorders such as trichotillomania and neurodermatitis

Surgical Workshop: Clinical Pearls

Victoria Lazareth, MA, MSN, NP-C, DCNP

What are some important pearls when performing surgery?

  1. Have patient take a “selfie” to identify biopsy site for future reference;
Eliminating standing cones by placing lateral sutures will create an elegant biopsy scar;
  3. Know the anatomy prior to performing a biopsy or excision at the head or neck;
  4. Hold scalpel like a pencil at 90° angle to the skin;
  5. Excise to a uniform depth throughout the wound.

Psoriasis and Other Papulosquamous Eruptions: Clinical Pearls

Bruce Strober, MD, PhD

  1. The severity of psoriasis is based on BSA, location, impact on quality of life and presence of psoriatic arthritis.
  2. Patients diagnosed with psoriasis should also be assessed for psoriatic arthritis and other comorbidities.
  3. Psoriasis treatment is not stepwise.
  4. Choice of therapy depends on individual patient characteristics.
  5. Combination therapy may be desirable in some patients.
  6. Topical therapies are appropriate initial step for patients with MILD psoriasis.
  7. Patients failing to response to treatment or worsening symptoms, RETHINK the psoriasis diagnosis.
  8. Erythrodermic or exfoliative dermatitis needs aggressive therapeutic intervention.
  9. 90% of psoriasis patients with nail involvement also have psoriatic arthritis and may require systemic therapy.
  10. Monotherapy is easier, but combination therapy is more effective for patients with moderate to severe psoriasis.


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Emerging Therapies in Psoriasis: Clinical Pearls

Bruce Strober, MD, PhD

What’s new in the field of psoriasis? Dr Strober provides us with some clinical pearls…

  1. TNF-inhibitors cause weight gain.
  2. Ustekinumab does not cause weight gain.
  3. IL-23 inhibitors block p19 and are more specific than IL-12/23 inhibitors, which block p40.
  4. Apremilast achieves PASI75 in approximately 30% of patients after 16 weeks.
  5. IL-17 pathway inhibitors achieve PASI75 in approximately 80% of patients after 12-16 weeks.
  6. IL-17 pathway inhibitors may slightly increase the risk of mucocutaneous candidiasis.
  7. JAK kinase inhibitors will require monitoring for liver function, renal function, lipids and creatinine phosphokinase.
  8. JAK kinase inhibitors might increase the risk of varicella zoster infection.
  9. Apremilast treats psoriatic arthritis.
  10. Apremilast does not need laboratory monitoring.





New Drugs

Neal Bhatia, MD & Ted Rosen, MD

In this presentation from MauiDerm 2014, Dr Neal Bhatia, an Associate Clinical Professor at Harbor-UCLA Medical Center and Dr Ted Rosen, a Professor of Medicine at Baylor College of Medicine, bring us the latest information on drugs that are, or will be available to the practicing dermatologist.

Part 1

Neal Bhatia, MD

This information is extremely important, as dermatologists need to continue to stay up-to-date with regards to the new data and literature. As healthcare providers, it is imperative to pay attention to the serious drugs for a number of reasons, in that, many dermatologists are losing their skills and letting good medicine pass them by.


Apremilast is an inhibitor of PDE4 and is currently in phase III trials for a number of diseases, including ankylosing spondylitis, psoriasis, and psoriatic arthritis along with orphan status for Bechet’s disease. A published case report studying cutaneous lichen planus with apremilast (20 mg bid for 12 weeks then a four week holiday) (Paul et al. JAAD, 2013) demonstrated that 30 percent of the patients experienced a 2-grade improvement and all patients had some improvement. This is important because this data will help us to eventually learn the dose and how to titrate the drug. This study was; however, small in numbers, treatment time and dosages.

Apremilast was also studied in discoid lupus erythematosus (DLE). Remember that DLE is Th1 mediated and apremilast blocks the Th1 process by inhibiting the production of IL-12, 23 and Th-17. There is also subsequent suppression of the Th-1 and Th-17 profile. Eight patients started in the study and four patients finished the 85-day course.  There were some gastrointestinal side effects and sensory neuropathy. (DeSouza et al. JDD, 2012) This indicates a need for larger studies.


There is a lot of good data demonstrating that sub-cutaneous omalimuzab shows promising results for the treatment of chronic idiopathic urticaria with the treatment spaced four weeks apart. The best data was with the 300mg dose, whereby the patients received the four weeks and then were observed for 16 weeks. Most of the patients had very good severity scores as well as significant reduction. For patients with severe chronic urticaria who are done with antihistamines, cannot handle topicals, and do not know the triggers, omalizumab plays a promising role.

Dr Bhatia commented on the new treatments for onychomycosis and feels that we have a “flood year of antifungals this year.” What we need to know:

  • Naftifine 2% gel—data suggest that there is residual active drug available in the stratum corneum even up to 4 weeks after treatment
  • Luliconazole is approved for the treatment of tinea pedis
  • Efinaconazole and Tavaborole are not approved as yet—but the data for both medications show promise
  • Itraconazole 200 mg tablets with new dosing protocol—coincidentally around the time of the oral ketoconazole black box warning
  • Ketoconazole gel (Xolegel) for use on the face and Itraconazole tablets (Onmel) are back
  • Econazole Foam is coming and the data is encouraging with a new vehicle

In a Phase II study of luliconazole cream 1 percent for the treatment of interdigital tinea pedis, the researchers found that complete clearance was 26.8 percent and 45.7 percent in subjects in the two-week and four-week treatment group, two weeks post-treatment. The antifungal effect persisted several weeks post-treatment resulting in increased rates of mycologic and clinical cure. Four weeks post-treatment, complete clearance rates were 53.7 percent and 62.9 percent, respectively.

Screen Shot 2014-03-20 at 2.24.26 PM


Niwano and colleagues looked at in vitro and in vivo antidermatophyte activities of luliconazole and found that it exhibited strong antifungal activity against Trichophyton spp with minimum inhibitory concentrations one to four times lower than lanoconazole or terbinafine. They also found that seven-day topical therapy (0.5% solution) was more effective than lanoconazole or terbinafine (0.5%) and luliconazole was the only drug that achieved complete mycologic cure with a three-day therapy.

Efinaconazole inhibits fungal lanosterol 14α-demethylase, which is involved in ergosterol biosynthesis at concentrations below minimum inhibitory concentrations. Efinaconazole is 4.8 times more potent than itraconazole in inhibiting ergosterol biosynthesis in T. mentagrophytes and is 7.3 times more potent than clotrimazole in C. albicans. Data on efinaconazole for toenail onychomycosis show favorable efficacy.  The chart below demonstrates that you do not need occlusion to see any benefit with efinaconazole.

Screen Shot 2014-03-20 at 2.24.43 PM


Tavaborole, representing a new class of anti-fungals, i.e., a novel boron-based compound, met all primary and secondary endpoints in the treatment of nail fungus when compared to ciclopirox lacquer in two studies and more importantly, demonstrated a negative culture of 87.0 percent vs 47.9 percent and 85.4 percent vs 51.2 percent, respectively. We will begin to see more and more phase III data in the near future.

Ketoconazole gel 2 percent has the same side effect precautions as oral products, on label, but these are doubtful. It’s important to remember that the brand name in some markets may be cheaper than the generic. Also of importance, rates of mycological cure and effective treatment (secondary efficacy endpoints) were observed in the Econazole Nitrate Foam 1% group relative to the Foam Vehicle in both phase 3 studies (P<0.001).

Itraconazole (200 mg) (OMNEL) utilizes Metrex® technology which improves bioavailability. It is now available with a new dosing protocol, which is more convenient for patients.  In one study, itraconazole (200 mg tablets) demonstrated statistically significant efficacy across all endpoints compared to vehicle at week 52 and was found to be noninferior to itraconazole 100-mg capsules at 52 weeks. The treatment duration of 12 weeks allows for 40-week follow-up. Remember that the nail grows out one tenth of a millimeter per day; therefore, every patient who is on any drug will not get a new nail for two hundred days. So, follow-up can be a slower process. The safety profile of Omnel is not statiscially different from that of itraconazole; however, there is a slight elevation in ALT.

Part 2

Dr Rosen continues the presentation with more dermatologic treatment advancements….

Pliagils (Lidocaine 7% + Tetracaine 7% Cream) is a topical, local analgesia for superficial dermatological procedures, such as filler injection, PDL or mild laser abrasion, and tattoo removal, which requires a longer application time. Pliaglis is self-occluding and forms a pliable peel. It is applied 20-30 minutes for most minor procedures and 60 minutes for more major procedures and is available in 30,60 and100gm tubes. A dosing chart is available pending on what area you are trying to anesthetize.

Sitavig (acyclovir 50mg Buccal) is indicated for recurrent oro-labial HSV. The Novel Lauriad® technology is a natural polymer derived from milk which adheres to the mucosa; therefore leading to high local drug concentration, but minimal blood levels. It is one tablet, applied within one hour of prodrome onset, on the upper gum at the incisor on the same side as the HSV lesion. After holding pressure for 30 seconds, the patient should allow the tablet to remain until it falls off (approximately six hours). Sitavig has shown to reduce the duration of an attack by 0.5 days based upon a randomized controlled trial of 775 patients.

Another advancement includes the approval of carbinoxamine maleate susp (Karbinal ER), which is a mildly sedating H1 antihistamine in an extended release formulation. It is used for the treatment of allergic rhinitis and conjunctivitis, uncomplicated urticaria, angioedema, and dermatographism. The advantages of this drug are that it is in a liquid form and there is infrequent dosing (2 times per day). It is also indicated for children as young as age two.

Vashe Skin and Wound Hydrogel, an aqueous-based, emollient containing, non-oily hydrogel, is a hypochlorous acid-containing material. It is intended to relieve pruritus, burning or pain from atopic, allergic contact and radiation dermatitis, as well as thermal burns. The drug maintains a moist environment, encourages autolytic digestion and prevents contamination. It works through the chlorination of histamine, leading to a less active derivative. It oxidizes many groups and subsequently directly and indirectly neutralizes the effects of cytokines, leukotrienes, alpha-1 antiproteinases, and cysteine proteases. This product is Aurstat with which you may already be familiar. It came from a partnership between PuriCore and Onset Dermatologics.

Old Drugs, New News:

  • Adapalene/BPO 1.2%/2.5% (Epiduo®)–Now FDA approved down to age 9
  • Desoximetasone 0.25% (Topicort®) –Now available as a spray
  • Ketoconazole 200mg tab (Nizoral®) –Severe limitations on use due to liver and adrenal toxicity, as well as drug interactions
  • Certolizumab pegol (Cimzia®) –Now approved for psoriatic arthritis, maybe psoriasis at some time in the future

Certolizumab Pegol (Cimzia®)

Cimzia is approved for the treatment of psoriatic arthritis (PsA) at 200mg sq QOW.  A phase III, multi-center, randomized, double-blind, controlled trial (RAPIDTM-PsA study) looked at 409 patients with adult onset PsA. The loading dose was 400mg or placebo at baseline, week two and week four, followed by 200mg qowk, 400mg q4wk, or placebo qowk. Adverse events were found in 62 percent of the patients versus 68 percent (placebo). ACR 20, 50, and 70 response rates at weeks 12 and 24 were higher for each Cimzia dose group relative to placebo; however, patients treated with Cimzia 200mg every other week demonstrated greater reduction in radopgraphic progression at week 24. Patients treated with Cimzia 400mg every four weeks did not demonstrate greater inhibition of radiographic progression at week 24, compared with placebo-treated patients.

Screen Shot 2014-03-20 at 2.24.57 PM

Overall, treatment with Cimzia resulted in improvement in skin manifestations in patients with PsA (62.2 percent to PASI 75). It is important, as dermatologists, to recognize that the safety and efficacy of Cimzia in the treatment of patients with plaque psoriasis has not been formally established and the use in psoriasis is off-label.

In conclusion, clinicians should pay special attention to the Nizoral FDA warnings published in July of 2013. ( The FDA states that:

  • Oral ketoconzazole should not be used as first-line therapy for ANY fungal infection
  • Ketoconazole should be used only for the treatment of life-threatening mycoses when the potential benefits outweigh the risks and alternative therapeutic options are not available or not tolerated
  • Oral ketoconazole is no longer indicated for dermatophyte or Candida infections
  • Oral ketoconazole is not indicated for fungal infections of the skin or nails
  • It is contraindicated in anyone with liver disease

If you use this drug and there is any hepatotoxic event, that could cause a great problem as a practitioner.

In summary, the dermatology landscape is continuing to grow with promising new drugs for our patients and it is imperative to stay on top of the latest data.

MauiDerm News Editor-Judy Seraphine




10 Clinical Pearls in Psoriasis

Bruce Strober, MD, PhD

Dr Strober, an expert in psoriasis, provides 10 clinical pearls from the psoriasis presentations presented at MauiDerm 2014.

  1. Psoriasis is associated with chronic kidney disease.
  2. Psoriasis is associated with 5-yr reduced life-expectancy.
  3. Psoriasis is more highly associated with diabetes risk than is rheumatoid arthritis.
  4. IL-17 inhibition is associated with very high efficacy.
  5. Ustekinumab is an IL-12/23 inhibitor that has some efficacy in psoriatic arthritis, but not as high an efficacy that is displayed by TNF-inhibitors.
  6. Apremilast is a PDE4 inhibitor that has efficacy in both psoriasis and psoriatic arthritis.
  7. Calcipotriene and calcitriol when used in combination with topical corticosteroids may reduce the risk of cutaneous atrophy.
  8. Topical corticosteroids only rarely induce adrenal suppression, even if used on areas of high percutaneous absorption.
  9. Psoriatic arthritis is present in 20-30% of psoriasis patients.
  10. Concomitant methotrexate reduces the immunogenicity and augments the efficacy of biologic therapies for psoriasis.